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瑞德西韦治疗COVID-19的最终报告
Remdesivir for the Treatment of Covid-19 — Final Report


John H. Beigel ... 呼吸系统疾病 • 2020.11.05
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摘要


背景

人们已经对治疗2019冠状病毒病(COVID-19)的多种药物进行了评估,但迄今评估的所有抗病毒药均被证实无效。

 

方法

我们开展了一项双盲、随机、安慰剂对照试验,目的是评估静脉输注瑞德西韦对确诊下呼吸道感染的COVID-19成人住院患者的疗效。患者被随机分配接受最多10天的瑞德西韦(第1天给予200 mg负荷剂量,之后每天给予100 mg,连续治疗最多9天)或安慰剂治疗。主要结局是恢复时间,其定义为出院或只是为了控制感染而住院。

 

结果

共计1,062例患者接受了随机分组(瑞德西韦组541例,安慰剂组521例)。瑞德西韦治疗组的中位恢复时间为10天(95%置信区间[CI],9~11),而安慰剂组为15天(95% CI,13~18)(恢复率比,1.29;95% CI,1.12~1.49;时序检验P<0.001)。其中一项分析采用比例优势模型进行分析,模型纳入8分等级量表;分析结果显示,在第15天时,瑞德西韦治疗组患者临床病情改善的可能性高于安慰剂组(针对疾病实际严重程度进行校正后,优势比,1.5;95% CI,1.2~1.9)。我们采用Kaplan-Meier曲线估计15天内死亡率,瑞德西韦组为6.7%,安慰剂组为11.9%;29天内的死亡率,瑞德西韦组为11.4%,安慰剂组为15.2%(风险比,0.73;95% CI,0.52~1.03)。瑞德西韦组532例患者中有131例(24.6%)报告了严重不良事件,安慰剂组516例患者中有163例(31.6%)报告了严重不良事件。

 

结论

本研究的结果证实,在确诊下呼吸道感染的COVID-19成人住院患者中,在缩短恢复时间方面,瑞德西韦优于安慰剂(由美国国立过敏和传染病研究所(National Institute of Allergy and Infectious Diseases)等资助;ACCT-1在ClinicalTrials.gov注册号为NCT04280705)。





作者信息

John H. Beigel, M.D., Kay M. Tomashek, M.D., M.P.H., Lori E. Dodd, Ph.D., Aneesh K. Mehta, M.D., Barry S. Zingman, M.D., Andre C. Kalil, M.D., M.P.H., Elizabeth Hohmann, M.D., Helen Y. Chu, M.D., M.P.H., Annie Luetkemeyer, M.D., Susan Kline, M.D., M.P.H., Diego Lopez de Castilla, M.D., M.P.H., Robert W. Finberg, M.D., Kerry Dierberg, M.D., M.P.H., Victor Tapson, M.D., Lanny Hsieh, M.D., Thomas F. Patterson, M.D., Roger Paredes, M.D., Ph.D., Daniel A. Sweeney, M.D., William R. Short, M.D., M.P.H., Giota Touloumi, Ph.D., David Chien Lye, M.B., B.S., Norio Ohmagari, M.D., Ph.D., Myoung-don Oh, M.D., Guillermo M. Ruiz-Palacios, M.D., Thomas Benfield, M.D., Gerd Fätkenheuer, M.D., Mark G. Kortepeter, M.D., Robert L. Atmar, M.D., C. Buddy Creech, M.D., M.P.H., Jens Lundgren, M.D., Abdel G. Babiker, Ph.D., Sarah Pett, Ph.D., James D. Neaton, Ph.D., Timothy H. Burgess, M.D., M.P.H., Tyler Bonnett, M.S., Michelle Green, M.P.H., M.B.A., Mat Makowski, Ph.D., Anu Osinusi, M.D., M.P.H., Seema Nayak, M.D., and H. Clifford Lane, M.D. for the ACTT-1 Study Group Members*
From the National Institute of Allergy and Infectious Diseases, National Institutes of Health (J.H.B., K.M.T., L.E.D., S.N., H.C.L.), and the Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences (T.H.B.), Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick (T. Bonnett), and Emmes, Rockville (M.G., M.M.) — all in Maryland; Emory University, Atlanta (A.K.M.); Montefiore Medical Center–Albert Einstein College of Medicine (B.S.Z.) and NYU Langone Health and NYC Health and Hospitals–Bellevue (K.D.), New York; University of Nebraska Medical Center, Omaha (A.C.K., M.G.K.); Massachusetts General Hospital, Boston (E.H.), and University of Massachusetts Medical School, Worcester (R.W.F.); University of Washington, Seattle (H.Y.C.), and Evergreen Health Medical Center, Kirkland (D.L.C.) — both in Washington; University of California, San Francisco, San Francisco (A.L.), Cedars–Sinai Medical Center, Los Angeles (V.T.), University of California, Irvine, Irvine (L.H.), University of California, San Diego, La Jolla (D.A.S.), and Gilead Sciences, Foster City (A.O.) — all in California; University of Minnesota (S.K.) and University of Minnesota School of Public Health and INSIGHT (J.D.N.), Minneapolis; University of Texas Health San Antonio, University Health System, and the South Texas Veterans Health Care System, San Antonio (T.F.P.), and Baylor College of Medicine, Houston (R.L.A.); Hospital Germans Trias i Pujol and irsiCaixa AIDS Research Institute, Badalona, Spain (R.P.); University of Pennsylvania, Philadelphia (W.R.S.); Medical School, National and Kapodistrian University of Athens, Athens (G.T.); National Center for Infectious Diseases–Tan Tock Seng Hospital–Lee Kong Chian School of Medicine–Yong Loo Lin School of Medicine, Singapore, Singapore (D.C.L.); the National Center for Global Health and Medicine Hospital, Tokyo (N.O.); Seoul National University Hospital, Seoul, South Korea (M.O.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City (G.M.R.-P.); the Department of Infectious Diseases, Amager Hvidovre Hospital–University of Copenhagen, Hvidovre (T. Benfield), and Rigshospitalet, Department of Infectious Diseases (CHIP) and INSIGHT, Copenhagen (J.L.) — both in Denmark; University Hospital of Cologne, Cologne, Germany (G.F.); Vanderbilt University Medical Center, Nashville (C.B.C.); and University College London, MRC Clinical Trials Unit at UCL and INSIGHT, London (A.G.B., S.P.). Address reprint requests to Dr. Beigel at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5601 Fishers Ln., Rm. 7E60, MSC 9826, Rockville, MD 20892-9826, or at jbeigel@niaid.nih.gov. *A complete list of members of the ACTT-1 Study Group is provided in the Supplementary Appendix, available at NEJM.org.

 

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